One of the major problems still confounding advances in modern ophthalmology is the seemingly irreversible and permanent nature of damage to the optic nerve.1 Severed axons of retinal ganglion cells, like the long tracts of the spinal cord, have no capacity for functional repair under normal physiological circumstances. This is most unfortunate, since a capacity for successful optic nerve regeneration is a necessity for restoration of vision following damage to the anterior visual pathway and might also open the door to future strategies of human whole eye transplantation. Influenced also by the tragic result of spinal cord transection, the topic of neuronal regeneration within the central nervous system (CNS) as a whole has become a most important area of medical research. Moreover, in the past few years, the extensive advances in neuroscience have made optic nerve (and spinal cord) regeneration a reality in laboratory mammals—either along existing pathways,2 3through peripheral nerve bridges,4 5 from embryonic transplants,6 7 or at certain critical stages of CNS development.8-10 The significance and implications of these advances should be considered in relation to developing a future clinical strategy for optic nerve regeneration in humans.

In this review I shall discuss the various problems associated with optic nerve regeneration. There are certain structural differences between optic nerve and spinal cord pathways, but regeneration studies in both systems have so far correlated well. In either case, three key issues remain the same: (1) if a lesioned neuron can survive the effects of axotomy; (2) if the surviving neuron can regrow an axon through the CNS environment; and (3) if the regrowing axon can be guided back appropriately to its original target to reform patterned connections. As we shall see, the first two of these criteria have been successfully overcome in various …